Preclinical
testing ( 1982 – 1990 ) on laboratory animals
to prove safe
use of preparation, indicated that the SEMAX®
is free from hormonal or doping effects, is not toxic, does
not evoke the habituation syndrome and meets the standards
and requirements for use in public health.

Clinical
Trials ( 1990-1994 ).
303 patients were tested in Military
hospitals. 200 patients were treated with SEMAX®
and 103 patients were treated with conventional treatment
(without SEMAX®).
A double–blind placebo controlled- type test was applied
on 59 patients, among whom one group of patients was administered
SEMAX® and the other group a placebo.
This trial, which lasted for 4 years, proved that SEMAX®
could be used in hospitals and polyclinics for treatment
and rehabilitation of patients with intellectual and memory
disturbances, and to improve the mental working capacities
of normal, healthy persons working under great mental and
physical stress conditions

Clinical
Trials ( 1994-1996 ).
These Trials lasted 2 years and involved several thousand
patients in medical centers around the Russian Federation.
It was shown that SEMAX® met all standards
and requirements for use in public health, and its mode
of action as a neuroactive regulatory peptide was achieved
without evoking any side effects.

Research
and Development
The neuroactive properties of short fragments of ACTH (Adenocorticotropic
Hormone) are well documented. The Dutch scientists D
de Wied and J.Jolles, Van
Reizen et al, observed non-specific activation
of the brain, in which non-specific processes of memory
(motivation, attention, sensitivity/irritability) are strengthened,
or to the inclusion of fragments of ACTH into specific memorizing
processes (consolidation, strengthening of memory).

Using
the fragment ACTH(4-10) (Met-Glu-His-Phe-Arg-Trp-Gly)
scientists discovered through the process of dissociation
of the amino acids and utilizing substitution and special
linkages, a peptide which was free from any hormonal effects
but possessed neuroactive endogenous modulatory and regulatory
properties, the sum of which manifested in a significant
neuroprotective effect against ischemic insults.

The
compound which was named SEMAX® consisted
of the bioactive portion of
ACTH4-10, : Met-Glu-His-Phe, and the substitution
of Arg-Trp-Gly with: Pro-Gly-Pro.
The P-G-P binding resulted in much improved stability due
to increased resistance towards blood peptidases.
In essence the molecule became :Pro8-Gly9-Pro10 ACTH(4-10) or ACTH(4-7) Pro-Gly-Pro.
Another novel approach was the method of administration,
although a much improved resistance towards peptidases had
been achieved through the PGP binding, the relatively small
size of the molecule allowed utilization of the route by
retrograde axonal transport through the N.Olfactorius or
N.Trigeminus, by administering

SEMAX®
as a solution/drops onto the nasal mucosa or sublingual
mucosa.
Adan A.R et al, and Gozes I observed excellent results administering
peptides through the intranasal route and concentrations
two to threefold those achieved by the I.V route have been
reported. The combination of avenues of access to the brain
via the retrograde axonal transport and microcirculation
routes contribute towards the achievement of significant
concentrations of the substance in the brain in a relatively
short period (1-3 minutes) and a significant duration of
therapeutic effect (20 hours).